Severe tumoral calcinosis in patient with chronic kidney disease

Tumoral calcinosis is a rare condition characterized by the deposition of calcium material in extra-articular soft tissues taking a tumoral form. It can be primary or secondary. The chronic kidney disease is among cause of metastatic calcications but the extensive periarticular cyst-like calcium salt containing space-consuming lesions in the form of tumoral calcinosis is very rare. Different factors predispose the dialysis patient to calcium salt deposits. We report a case of 61 years-old-patient with chronic kidney disease under periodic hemodialysis due to hypertensive nephropathy who developed mechanical pain, evolving since three months, in the left hip, the upper extremity of the right leg and both shoulders with swelling and limited movement interfering with daily activity. The severe TC was diagnosed by the radiography and MRI requiring the modication of treatment strategy.


Introduction
Tumoral calcinosis (TC), a very rare disease entity, occurred in the described patient with end-stage renal disease (ESRD) due to disturbed calcium phosphate metabolism, in which a calci ed mass grows around a large joint, and can occur in patients undergoing renal dialysis (1). It is characterized by the deposition of calcium material in the periarticular soft tissues. It can be familial, idiopathic or secondary, especially to chronic kidney disease with or without hemodialysis (2). Clinically, the swelling is rm, mobile in relation to the skin, usually asymptomatic, it can be responsible for joint stiffness and bone pain (3). It can be single or multiple. The diagnosis is radiological, made by plain radiography. Ultrasound shows a polylobed, hyperechoic appearance with a characteristic calci ed peripheral shell. Magnetic resonance imaging is a better exploration (4). Increased dialysis, especially daily dialysis, can reduce calci cations, but especially transplantation is the best treatment. Treatment of tumor calcinosis is sometimes surgical.
While soft tissue calci cations in patients with ESRD is common, the prevalence of extensive periarticular cyst-like calcium salt containing space-consuming lesions in the form of tumoral calcinosis is very rare.
We report a case of extensive TC occurring in an hemodialysis ESRD patient.

Case Report
A 61-year-old patient. He is followed, since 15 years, for high blood pressure complicated three years ago by hypertensive nephropathy for which he is under periodic hemodialysis, three times a week. He consults for mechanical pain in the left hip, the upper extremity of the right leg and both shoulders with swelling and limited range of motion in the right shoulder interfering with daily activity and evolving since three months. The physical examination showed a rounded mass at the anterior and supero-external right shoulder side, with regular contours, farm and mobile measuring 7 cm, along the deltoid muscle curve without local in ammatory skin signs ( Figure 1A). In the right leg, the mass has the same characteristics, located on the supero-external side ( Figure 1B). The mobility of knee was painful without limitation.The rest of the joint's exam, especially the two hips was normal. Imaging examinations revealed, at plain radiograph, severe manifestation of tumoral calcinosis: polycyclic, heterogeneous formations in the periarticular space of the 2 shoulders especially on the right one, voluminous and extending to the level of the deltoid, the bursa under acromio-deltoid, supra-spinous and subscapular fossae, without bone erosion (Figure 2A). In the right knee, there is a multiple calci cations of the superior and postero-external soft tissue, at the proximal part of the internal collateral ligament, without focal bone lesion ( Figure 2B). The MRI showed multiple macro-calci cations in the periarticular space of the 2 shoulders, especially on the right one. They occupy the synovium and peripheral muscles, in particular the deltoid, respecting the bone structures with uid levels. These calci ed formations are hypointense in T1, heterogeneous hypersignal with central areas of hyposignal in T2 (Figures 2C and D).The blood test results in admission found disturbance renal fonction : creatinemia at 94.30 mg / l, urea at 1.82 g / l. The calcium was normal at 103 mg / l with hyperphosphatemia at 71 mg / l, hyperparathyroidism at 128.50 pg / ml. Uric acid was at 69 mg / l. The aluminum level was normal. His calcitriol was at the lower reference range at 27 ng/ml.The nal diagnosis of the patient was secondary TC due to ESRD with secondary hyperparathyroidism and hyperphosphatemia.
Due to the severity of the clinical and radiological ndings, and because the patient refused at this stage any surgery, his hemodialysis schedule and number sessions have been increased, with low-calcium and low-phosphate diet advice. The follow-up radiography is expected in 3 moths with control of laboratory examinations. The parathyroidectomy will be proposed if there will not be no response to this rst treatment strategy.

Discussion
Tumoral calcinosis is a rare benign disease characterized by the deposition of calcium material in extraarticular soft tissues taking a tumoral form. It can be primary or secondary. Chronic renal failure in ESRD is one of the causes of metastatic calci cations (1,5). The prevalence of TC in hemodialysis patients has been reported to range from 0.5% to 1.9% (6).
The pathophysiology underlying the development of this disease entity remains unclear. It is mostly associated with manifestation of tertial hyperparathyroidism, hypercalcemia and hyperphosphatemia.
The other factors predisposing the patient to calcium salt deposits in outside of hyperparathyroidism and elevation of phosphocalcic product are: excess intake of calcium or vitamin D, poor compliance of the patient with regular intake of chelators, dialysis insu cient or a dialysate rich in aluminum (7).
Otherwise, the soft tissue calci cation is considered secondary TC in patients with also pseudoxanthoma elasticum, malignancy, sarcoidosis, primary hyperparathyroidism, scleroderma, hypervitaminosis D, milk-alkali syndrome, or massive osteolysis (6). The periarticular calci cations may be accompanied by an aseptic in ammatory tissue reaction with encapsulation of the crystals. They are common on the hips, shoulders, knees, elbows, wrists and ngers. An homogeneous calci ed pre-articular mass of soft tissues, with respect to the joint space without bone damage is the typical radiographic appearance (4).
Diagnosis of TC is mainly based on imaging modalities. Plain radiographs show the typical appearance of amorphous, multilobulated and cystic calci cations in a peri-articular location. The CT-Scan is useful to appreciate the relationship of the tumor with the other organs just like the MRI which visualizes in addition the multiple cavities and the uid levels. Single-photon emission tomography / CT hybrid imaging (PET-scan) mainly allows the identi cation of other subclinical joint or visceral locations in a single examination (6,8,9,10). Histology, when performed, nd multiple lobules of calci ed masses separated by septa of brous tissue surrounded by lymphocytes and giant cells (5).
The clinical context and the radiological data made the diagnosis of TC in our patient due to ESRD under dialysis. The rarity of this entity, the severity and the early onset of TC in secondary hyperparathyroidism state are the originality of this clinical case.
The global management is based on the correction of the calcium and phosphate product. The reduction or even the disappearance of calci cations go through the correction of hyperparathyroidism or the increase of dialysis sessions with low-Ca dialysate, while checking the aluminum level in the dialysate.
Parathyroidectomy is one of the therapeutic options (11,12). Kidney transplantation can promote rapid decrease in calci cations and is indicate in cases of severe calcinosis. Surgery ,with complete resection, is recommended when there is a risk of vascular damage or on joint mobility (1,3,4).

Conclusion
We report a patient with ESRD under hemodialysis and severe tumoral calcinosis. It is important for rheumatologist and renal health care providers to recognize that ESRD patients may develop this rare disease entity to differentiate them to other causes of TC and in patient with ESRD to TC mimicking tophi. TC patients, including this case, should be checked regularly to keep their serum phosphate levels low, and radiologically assessed. The improvement of the treatment strategy and reinforcement of patient compliance are important for the complete remission.